血管内皮生长因子165和肝细胞生长因子促心肌梗死后心肌细胞增生机制的研究

摘要

Objective: To investigate the mechanism of vascular endothelial growth factor ( VEGF)165 and hepatocyte growth factor (HGF) improving cardiomyocyte proliferation in experimental porcine after myocardial infarction (MI). Methods: The MI model was established by left anterior descending artery ligation in 15 male pigs and the animals were divided into 3 groups, n=5 in each group. Control group, the pigs received normal saline injection at the infarct and peri-infarct zones. VEGF group, the pigs received (1×1010 ) pfu of viral titers of Ad-VEGF injection. HGF group, the pigs received (1×1010 ) pfu of viral titers of Ad-HGF injection. The myocardial perfusion and cardiac function were examined by SPECT, the protein expressions of VEGF165 and HGF were measured by Western blot analysis, cardiomyocyte proliferation was analyzed by immunolfuorescence and immunoprecipitation method. Results: ① Compared with Control group, the expressions of VEGF165 and HGF were higher at the infarct and peri-infarct zones in both treatment groups; ② Both treatment groups had better cardiac function and myocardial perfusion; ③ Both treatment groups had improved cardiomyocyte proliferation at the infarct and peri-infarct zones.④VEGF165 promoted cardiomyocyte proliferation via p27 pathway;⑤HGF promoted cardiomyocyte proliferation via p21 and p27 pathways. Conclusion: VEGF165 and HGF could improve myocardial perfusion and function in experimental porcine after MI, VEGF165 and HGF promote cardiomyocyte proliferation via different pathways.%目的：探讨血管内皮生长因子165（VEGF165）和肝细胞生长因子（HGF）促进心肌梗死后心肌细胞增生机制的异同。　　方法：将15头雄性中华小型猪结扎冠状动脉左前降支构建心肌梗死模型。实验动物分成三组：对照组、VEGF基因重组腺病毒载体组（Ad-VEGF组）、HGF基因重组腺病毒载体组（Ad-HGF组），每组5只。将1×1010pfu的Ad-VEGF和Ad-HGF分别局部注射到Ad-VEGF组和Ad-HGF组猪的心肌梗死周围区，相同剂量的生理盐水注射到对照组。通过门控单光子发射计算机成像仪检测心肌灌注和心脏功能，通过免疫印迹法检测VEGF165和HGF在心肌的表达，采用免疫荧光双染和免疫共沉淀分析心肌细胞增生。　　结果：①在Ad-VEGF组，心肌梗死区和梗死周围区的VEGF165表达明显高于正常心肌（P<0.01）；在Ad-HGF组，心肌梗死区和梗死周围区的HGF表达明显高于正常心肌（P<0.01）。②高表达的VEGF165和HGF改善梗死后心肌灌注和心脏功能。③VEGF165和HGF可促进梗死区和梗死周围区心肌细胞增生。④VEGF165通过p27促心肌细胞增生。⑤HGF通过p21和p27促心肌细胞增生。　　结论：VEGF165和HGF改善梗死后心肌灌注和心脏功能，促心肌细胞增生，但VEGF165和HGF促心肌细胞增生途径不同。